title: Enkephalin downregulation in the nucleus accumbens underlies chronic stress-induced anhedonia.
abstract: Restraint and immobilization have been extensively used to study habituation of the neuroendocrine response to a repeated stressor, but behavioral consequences of this stress regimen remain largely uncharacterized. In this study, we used sucrose preference and the elevated-plus maze to probe behavioral alterations resulting from 14 days of restraint in rats. We observed a decrease in sucrose preference in stressed animals, particularly in a subgroup of individuals, but no alteration in anxiety behaviors (as measured in the elevated-plus maze) four days following the last restraint. In these low-sucrose preference animals, we observed a downregulation of the expression of preproenkephalin mRNA in the nucleus accumbens. Furthermore, we observed a strong correlation between enkephalin expression and sucrose preference in the shell part of the nucleus accumbens, with a lower level of enkephalin expression being associated with lower sucrose preference. Interestingly, quantification of the corticosterone response revealed a delayed habituation to restraint in the low-sucrose preference population, which suggests that vulnerability to stress-induced deficits might be associated with prolonged exposure to glucocorticoids. The induction of ΔFosB is also reduced in the nucleus accumbens shell of the low-sucrose preference population and this transcription factor is expressed in enkephalin neurons. Taken together, these results suggest that a ΔFosB-mediated downregulation of enkephalin in the nucleus accumbens might underlie the susceptibility to chronic stress. Further experiments will be needed to determine causality between these two phenomena.
authors.affiliation: Centre de recherche du CHU, Axe Neurosciences and Université Laval , Québec, QC , Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Poulin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Laforest
authors.forename: Guy
authors.initials: G
authors.lastname: Drolet
mesh_terms: D059445:Anhedonia / Q000502:physiology*; D000818:Animals; D015536:Down-Regulation; D004745:Enkephalins / Q000096:biosynthesis*; D005518:Food Preferences; D006185:Habituation, Psychophysiologic; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D004745:Enkephalins; C483820:Fosb protein, rat; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013395:Sucrose; C033660:preproenkephalin